A Modified Simplified Frailty Score Predicts Survival, Toxicity, and Treatment Selection in Elderly Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Cohort Study

Background/Objectives: Treatment decisions for elderly patients with diffuse large B-cell lymphoma (DLBCL) often rely on subjective clinical impression rather than systematic frailty assessment. We evaluated whether a modified simplified frailty score (mSFS)—a binary adaptation of the Isaksen score—predicts treatment selection, toxicity, and survival. Methods: In this retrospective study of 117 patients aged ≥65 years with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or dose-attenuated R-CHOP (R-mini-CHOP) at MedStar Health community hospitals (2000–2025), the mSFS assigned one point each for age ≥80, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, and ≥5 comorbidities; score ≥2 defined frailty. Results: Among 86 R-CHOP recipients, 17 (19.8%) were mSFS-frail; among 31 R-mini-CHOP recipients, 15 (48.4%) were mSFS-fit. In R-CHOP recipients, frailty independently predicted worse overall survival (adjusted hazard ratio [aHR] 7.67, 95% confidence interval [CI] 2.36–24.97), progression-free survival (aHR 2.90, 95% CI 1.18–7.13), grade ≥3 adverse events (adjusted odds ratio [aOR] 3.90, p = 0.035), and early discontinuation (aOR 4.41, p = 0.034). Frail R-CHOP patients had lower complete response rates (aOR 0.24, p = 0.038). Fit R-mini-CHOP patients had 88% lower odds of complete response versus fit R-CHOP patients (aOR 0.12, p = 0.003). Among R-mini-CHOP recipients, frailty was not significantly associated with outcomes. Conclusions: The mSFS revealed bidirectional discordance with oncologist-assessed frailty and independently predicted survival, toxicity, and response, supporting its integration into community oncology practice.